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3.
Braz Oral Res ; 34: e005, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32022224

RESUMO

The purpose of this study was to evaluate the effect of ionizing radiation from high energy X-ray on fluoride release, surface roughness, flexural strength, and surface chemical composition of the materials. The study groups comprised five different restorative materials: Beautifil II, GCP Glass Fill, Amalgomer CR, Zirconomer, and Fuji IX GP. Twenty disk-shaped specimens (8x2 mm) for fluoride release and 20 bar-shaped specimens (25 x 2x 2 mm) for flexural strength were prepared from each material. Each material group was divided into two subgroups: irradiated (IR) and non-irradiated (Non-IR). The specimens from IR groups were irradiated with 1.8 Gy/day for 39 days (total IR = 70.2 Gy). The amount of fluoride released into deionized water was measured using a fluoride ion-selective electrode and ion analyzer after 24 hours and on days 2, 3, 7, 15, 21, 28, 35, and 39 (n = 10). The flexural strength was evaluated using the three-point bending test (n = 10). After the period of measurement of fluoride release, seven specimens (n = 7) from each group were randomly selected to evaluate surface roughness using AFM and one specimen was randomly selected for the SEM and EDS analyses. Data were analyzed with two-way ANOVA and Tukey tests (p = 0.05). The irradiation significantly increased fluoride release and surface roughness for Amalgomer CR and Zirconomer groups (p < 0.05). No significant change in flexural strength of the materials was observed after irradiation (p > 0.05). The ionizing radiation altered the amount of fluoride release and surface roughness of only Amalgomer CR and Zirconomer. The effect could be related to the chemical compositions of materials.


Assuntos
Apatitas/efeitos da radiação , Bis-Fenol A-Glicidil Metacrilato/efeitos da radiação , Resinas Compostas/efeitos da radiação , Fluoretos/química , Cimentos de Ionômeros de Vidro/efeitos da radiação , Radiação Ionizante , Zircônio/efeitos da radiação , Análise de Variância , Apatitas/química , Bis-Fenol A-Glicidil Metacrilato/química , Resinas Compostas/química , Resistência à Flexão , Cimentos de Ionômeros de Vidro/química , Teste de Materiais , Microscopia Eletrônica de Varredura , Valores de Referência , Reprodutibilidade dos Testes , Espectrometria por Raios X , Estatísticas não Paramétricas , Propriedades de Superfície/efeitos da radiação , Fatores de Tempo , Zircônio/química
4.
Expert Opin Pharmacother ; 21(3): 317-337, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31928256

RESUMO

Introduction: There is a limited array of currently available medicinals that are useful for either the prevention, mitigation or treatment of bodily injuries arising from ionizing radiation exposure.Area covered: In this brief article, the authors review those pharmacologic agents that either are currently being used to counter the injurious effects of radiation exposure, or those that show promise and are currently under development.Expert opinion: Although significant, but limited progress has been made in the development and fielding of safe and effective pharmacotherapeutics for select types of acute radiation-associated injuries, additional effort is needed to broaden the scope of drug development so that overall health risks associated with both short- and long-term injuries in various organ systems can be reduced and effectively managed. There are several promising radiation countermeasures that may gain regulatory approval from the government in the near future for use in clinical settings and in the aftermath of nuclear/radiological exposure contingencies.


Assuntos
Lesões por Radiação/tratamento farmacológico , Radiação Ionizante , Protetores contra Radiação/administração & dosagem , Animais , Humanos
5.
Life Sci ; 244: 117342, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31978450

RESUMO

AIMS: Microvascular endothelial cell dysfunction is a leading cause of radiation-induced heart disease (RIHD). BRCA1 plays an important role in DNA damage repair. The study aims to explore the effect of BRCA1 in endothelial cells involved in RIHD. MATERIALS AND METHODS: BRCA1 and p21 expression were detected in human umbilical vein endothelial cells (HUVECs) and in mouse heart tissue after irradiation exposure. The effects of BRCA1 on cell proliferation, cell cycle and radiosensitivity were determined in HUVECs with overexpression and knockdown of BRCA1. A mouse model of RIHD was established. Heart damage was detected in C57BL/6J mice and endothelial cell specific knockout BRCA1 mice (EC-BRCA1-/-). KEY FINDINGS: BRCA1 and p21 expression was significantly increased both in vitro and vivo response to irradiation. BRCA1 overexpression in endothelial cells enhanced cell growth and G1/S phase arrest, and the opposite results were observed in BRCA1 knockdown endothelial cells. BRCA1 downregulated endothelial cell cycle-related genes cyclin A, cyclin D1, cyclin E and p-Rb through increasing p21 expression, and HUVECs with BRCA1 gene knockdown were more sensitive to radiation. In vivo, a decrease in cardiac microvascular density, as well as cardiomyocyte hypoxia and apoptosis were observed in a time-dependent manner. EC-BRCA1-/- mice were more prone to severe RIHD than EC-BRCA1+/- mice after 16Gy radiation exposure due to endothelial dysfunction caused by loss of BRCA1, and p21 was declined in EC-BRCA1-/- mice heart. SIGNIFICANCE: These findings indicate that BRCA1 plays a protective role in RIHD by regulating endothelial cell cycle arrest mediated by p21 signal.


Assuntos
Proteína BRCA1/metabolismo , Pontos de Checagem do Ciclo Celular , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Neovascularização Patológica/prevenção & controle , Substâncias Protetoras/administração & dosagem , Tolerância a Radiação , Animais , Proteína BRCA1/genética , Proteína BRCA1/fisiologia , Proliferação de Células , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos da radiação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Patológica/etiologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Radiação Ionizante
6.
Br J Radiol ; 93(1107): 20190494, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31687835

RESUMO

Clinical parameters and empirical evidence are the primary determinants for current treatment planning in radiation oncology. Personalized medicine in radiation oncology is only at the very beginning to take the genetic background of a tumor entity into consideration to define an individual treatment regimen, the total dose or the combination with a specific anticancer agent. Likewise, stratification of patients towards proton radiotherapy is linked to its physical advantageous energy deposition at the tumor site with minimal healthy tissue being co-irradiated distal to the target volume. Hence, the fact that photon and proton irradiation also induce different qualities of DNA damages, which require differential DNA damage repair mechanisms has been completely neglected so far. These subtle differences could be efficiently exploited in a personalized treatment approach and could be integrated into personalized treatment planning. A differential requirement of the two major DNA double-strand break repair pathways, homologous recombination and non-homologous end joining, was recently identified in response to proton and photon irradiation, respectively, and subsequently influence the mode of ionizing radiation-induced cell death and susceptibility of tumor cells with defects in DNA repair machineries to either quality of ionizing radiation.This review focuses on the differential DNA-damage responses and subsequent biological processes induced by photon and proton irradiation in dependence of the genetic background and discusses their impact on the unicellular level and in the tumor microenvironment and their implications for combined treatment modalities.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA/fisiologia , Fótons/uso terapêutico , Medicina de Precisão , Terapia com Prótons , Eficiência Biológica Relativa , Absorção de Radiação , Animais , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral/efeitos da radiação , Terapia Combinada , Reparo do DNA por Junção de Extremidades , Humanos , Transferência Linear de Energia , Neoplasias/genética , Neoplasias/radioterapia , Órgãos em Risco/efeitos da radiação , Tolerância a Radiação/genética , Radiação Ionizante , Microambiente Tumoral
7.
J Environ Radioact ; 211: 105757, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29970267

RESUMO

Single species laboratory tests and associated species sensitivity distributions (SSDs) that utilise the resulting data can make a key contribution to efforts to prospective hazard assessments for pesticides, biocides, metals and ionising radiation for research and regulatory risk assessment. An assumption that underlies the single species based toxicity testing approach when combined in SSD models is that the assessments of sensitivities to chemical and ionising radiation measured across a range of species in the laboratory can inform on the likely effects on communities present in the field. Potential issues with the validity of this assumption were already recognised by Van Straalen and Denneman (1989) in their landmark paper on the SSD methodology. In this work, they identified eight major factors that could potentially compromise the extrapolation of laboratory toxicity data to the field. Factors covered a range of issues related to differences in chemistry (e.g. bioavailability, mixtures); environmental conditions (optimal, variable), ecological (compensatory, time-scale) and population genetic structure (adaptation, meta-population dynamics). This paper outlines the evidence pertaining to the influence of these different factors on toxicity in the laboratory as compared to the field focussing especially on terrestrial ecosystems. Through radiological and ecotoxicological research, evidence of the influence of each factor on the translation of observed toxicity from the laboratory to field is available in all cases. The importance of some factors, such as differences in chemical bioavailability between laboratory tests and the field and the ubiquity of exposure to mixtures is clearly established and has some relevance to radiological protection. However, other factors such as the differences in test conditions (optimal vs sub-optimal) and the development of tolerance may be relevant on a case by case basis. When SSDs generated from laboratory tests have been used to predict chemical and ionising radiation effects in the field, results have indicated that they may often seem to under-predict impacts, although this may also be due to other factors such as the effects of other non-chemical stressors also affecting communities at polluted sites. A better understanding of the main factors affecting this extrapolation can help to reduce uncertainty during risk assessment.


Assuntos
Monitoramento de Radiação , Ecossistema , Estudos Prospectivos , Radiação Ionizante , Medição de Risco , Testes de Toxicidade , Poluentes Químicos da Água
8.
J Environ Radioact ; 211: 105830, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30385053

RESUMO

The assessment of the ecological impact due to radionuclides at contaminated sites requires estimation of the exposure of wildlife, in order to correlate radiation dose with known radiological effects. The robust interpretation of field data requires consideration of possible confounding effects (e.g., from the tsunami at Fukushima) and an accurate and relevant quantification of radiation doses to biota. Generally, in field studies the exposure of fauna and flora has often been characterised as measurements of the ambient dose rate or activity concentrations in some components of the environment. The use of such data does not allow the establishment of a robust dose-effect relationship for wildlife exposed to ionising radiation in the field. Effects of exposure to radioactivity depend on the total amount of energy deposited into exposed organisms, which is estimated by adding doses (or dose rates) for all radionuclides and exposure pathways. Realistic dose estimation needs to reflect the entire story of the organisms of interest during their whole exposure period. The process of identifying and collecting all the related information should allow the "W" questions (Which organisms are exposed, Where, When and hoW) to be answered. Some parameters are well known to influence dose (rate): the organism life stage, its ecological characteristics (e.g. habitat, behaviour), the source term properties (e.g. discharging facility, nature of radiation), etc. The closer the collated data are to the ideal data set, the more accurate and realistic the dose (rate) assessment will be. This means characterising each exposure pathway (internal and external), the activity concentration in each exposure source, the time each organism spends in a given place, as well as the associated dose. In this paper the process of data collation in view of dose reconstruction is illustrated for Japanese birds exposed to radioactive deposition following the Fukushima accident. With respect to the Chernobyl Exclusion Zone we will also consider variability under field conditions, availability of relevant datasets and options for better estimating internal and external doses received by wildlife.


Assuntos
Exposição à Radiação , Monitoramento de Radiação , Radioatividade , Animais , Animais Selvagens , Doses de Radiação , Radiação Ionizante
9.
J Environ Radioact ; 211: 105870, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30578084

RESUMO

Ecological risk assessment has globally become the basis for environmental decision-making within government and industry for chemical substances. Regarding radioactive substances, recently revised International and European Basic Safety Standards are pushing the development of member state policy on environmental regulation in the field of radiological protection. Within this framework, existing derived effect benchmarks for ionising radiation and non-human species need to be more robust to reinforce their credibility when used as levels of exposure considered to be safe for the environment. Actually, the derivation of such benchmarks has mainly relied on laboratory studies from a limited number of species. Moreover lab species would be apparently less radiosensitive than for example terrestrial wildlife chronically exposed to ionising radiation in the Chernobyl Exclusion Zone. Additionally to the results of such comparison that still need to be confirmed, another way to challenge benchmarks is to improve the quality/quantity of radiotoxicity data constituting the basis for a statistically-based comparison. This is the major focus of this paper where we demonstrate through various examples how to make the comparison more robust (i) by analysing the discrepancy between lab and field at the taxonomic level rather than at the ecosystem level, (ii) by extending the knowledge base making use of acute radiotoxicity data, (iii) by identifying environmental factors modifying radiological dose-effect relationship in the field.


Assuntos
Tolerância a Radiação , Animais , Ecossistema , Exposição Ambiental , Monitoramento de Radiação , Radiação Ionizante
10.
Ann Agric Environ Med ; 26(4): 606-616, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31885235

RESUMO

INTRODUCTION AND OBJECTIVE: The tendency towards postponement of maternity implies a greater exposure of female germ cells to damaging environmental effects, including ionizing radiation (IR). Progress in paediatric oncology, based on the use of radiotherapy, also implies the occurrence of gonadal dysfunctions and subsequent female fertility disorders. Therefore, it seems justifiable to systematize the state of knowledge concerning the effect of IR on the female reproductive system. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: A considerable part of studies concerning the effect of IR on female germ cells have been conducted on animals. Their extrapolation to humans is hindered because in animal studies high acute exposures are applied, which do not reflect human environmental exposures characterized by chronic low dose exposure. Studies on animals provide a heterogenous image, which hinders the formulation of unequivocal conclusions and indicates that radiosensitivity depends, i.a. on IR dose, stage of development of oocytes, the applied marker of the effects of IR, or on the species. LD50 of human oocytes is estimated to be below 2 Gy. The effect of IR depends, i.a. on the dose fractionation and the age (older women are more radiosensitive). In females, the effective sterilizing dose is: at birth 20.3 Gy, at 10 years 18.4 Gy, at 20 years 16.5 Gy, whereas at 30 years 14.3 Gy, which is associated with the available pool of ovarian follicles. CONCLUSIONS: Within the range of low doses received as a result of environmental exposure to IR, there is no evidence for the occurrence of either adverse pregnancy outcomes, nor fertility disorders in females. These effects may be related to the cancer radiotherapy, or exposure to high IR doses during nuclear accidents.


Assuntos
Exposição à Radiação/efeitos adversos , Lesões por Radiação/fisiopatologia , Reprodução/efeitos da radiação , Animais , Feminino , Humanos , Óvulo/efeitos da radiação , Lesões por Radiação/etiologia , Radiação Ionizante
11.
Genes Dev ; 33(23-24): 1702-1717, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31699778

RESUMO

The establishment of polyubiquitin conjugates with distinct linkages play important roles in the DNA damage response. Much remains unknown about the regulation of linkage-specific ubiquitin signaling at sites of DNA damage. Here we reveal that Cezanne (also known as Otud7B) deubiquitinating enzyme promotes the recruitment of Rap80/BRCA1-A complex by binding to Lys63-polyubiquitin and targeting Lys11-polyubiquitin. Using a ubiquitin binding domain protein array screen, we identify that the UBA domains of Cezanne and Cezanne2 (also known as Otud7A) selectively bind to Lys63-linked polyubiquitin. Increased Lys11-linkage ubiquitination due to lack of Cezanne DUB activity compromises the recruitment of Rap80/BRCA1-A. Cezanne2 interacts with Cezanne, facilitating Cezanne in the recruitment of Rap80/BRCA1-A, Rad18, and 53BP1, in cellular resistance to ionizing radiation and DNA repair. Our work presents a model that Cezanne serves as a "reader" of the Lys63-linkage polyubiquitin at DNA damage sites and an "eraser" of the Lys11-linkage ubiquitination, indicating a crosstalk between linkage-specific ubiquitination at DNA damage sites.


Assuntos
Dano ao DNA , Reparo do DNA/genética , Endopeptidases/genética , Endopeptidases/metabolismo , Poliubiquitina/metabolismo , Transdução de Sinais/fisiologia , Linhagem Celular Tumoral , Dano ao DNA/efeitos da radiação , Proteínas de Ligação a DNA , Enzimas Desubiquitinantes/genética , Enzimas Desubiquitinantes/metabolismo , Técnicas de Silenciamento de Genes , Células HEK293 , Chaperonas de Histonas , Humanos , Lisina/metabolismo , Proteínas Nucleares , Análise Serial de Proteínas , Ligação Proteica , Domínios Proteicos , Transporte Proteico/genética , Radiação Ionizante
12.
BMC Health Serv Res ; 19(1): 841, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727071

RESUMO

BACKGROUND: In the context of increasing availability of computed tomography (CT) scans, judicious use of ionising radiation is a priority to minimise the risk of future health problems. Hence, education of clinicians on the risks and benefits of CT scans in the management of patients is important. METHODS: An educational message about the associated lifetime cancer risk of a CT scan was added to all CT scan reports at a busy acute teaching hospital in the UK. An online multiple choice survey was completed by doctors before and after the intervention, assessing education and knowledge of the risks involved with exposure to ionising radiation. RESULTS: Of 546 doctors contacted at baseline, 170 (31%) responded. Over a third (35%) of respondents had received no formal education on the risks of exposure to ionising radiation. Over a quarter (27%) underestimated (selected 1 in 30,000 or negligible lifetime cancer risk) the risk associated with a chest, abdomen and pelvis CT scan for a 20 year old female. Following exposure to the intervention for 1 year there was a statistically significant improvement in plausible estimates of risk from 68.3 to 82.2% of respondents (p < 0.001). There was no change in the proportion of doctors correctly identifying imaging modalities that do or do not involve ionising radiation. CONCLUSIONS: Training on the longterm risks associated with diagnostic radiation exposure is inadequate among hospital doctors. Exposure to a simple non-directional educational message for 1 year improved doctors' awareness of risks associated with CT scans. This demonstrates the potential of the approach to improve knowledge that could improve clinical practice. This approach is easily deliverable and may have applications in other areas of clinical medicine. The wider and longer term impact on radiation awareness is unknown, however, and there may be a need for regular mandatory training in the risks of radiation exposure.


Assuntos
Médicos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Exposição à Radiação/prevenção & controle , Tomografia Computadorizada por Raios X/efeitos adversos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Projetos Piloto , Doses de Radiação , Radiação Ionizante
13.
Ecotoxicol Environ Saf ; 186: 109764, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31610356

RESUMO

Crustaceans have been designated as internationally important model organisms in the development of environmental radioprotection measures. Despite the known sensitivity of sperm to ionizing radiation, the impacts of chronic radiation exposure on male fertility in crustaceans have not been studied. For the first time, the present study aimed to assess the impacts of chronic radiation exposure on male fertility, sperm DNA damage and concomitant impacts on breeding in two amphipod crustaceans. Echinogammarus marinus and Gammarus pulex (male fertility only) were exposed to phosphorus-32 at dose rates of 0, 0.1, 1 and 10 mGy/d and sperm parameters, DNA damage and knock-on impacts on breeding were assessed. Sperm quality parameters and DNA damage were assessed using a fluorescent staining method and single cell gel electrophoresis respectively. Concomitant effects of male exposure to radiation on fecundity were determined by pairing phosphorus-32 exposed males to unexposed sexually mature females. In E. marinus, a statistically significant reduction of 9 and 11% in the quality of sperm was recorded at dose rates of 1 and 10 mGy/d respectively, with no significant effects recorded on sperm counts. Conversely in the freshwater G. pulex, no significant impact of radiation on sperm quantity or quality was recorded. For E. marinus, a statistically significant increase in DNA damage was recorded at doses of 10 mGy/d. Reduced fecundity and an increase in the frequency of abnormal embryos was recorded in female E. marinus breeding with males exposed to radiation. These findings suggest sperm quality may be a sensitive indicator of radiation exposure in invertebrates with potential impacts on the unexposed embryo, though unclear dose-response and differences between two closely related species necessitate further study before robust conclusions can be drawn.


Assuntos
Anfípodes/efeitos da radiação , Dano ao DNA , Radiação Ionizante , Espermatozoides/efeitos da radiação , Anfípodes/genética , Anfípodes/crescimento & desenvolvimento , Animais , Feminino , Fertilidade/efeitos da radiação , Água Doce , Masculino , Água do Mar , Espermatozoides/patologia
14.
J Immunol Res ; 2019: 9645481, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565662

RESUMO

Purpose: Most tumours are characterized by an inflammatory microenvironment, and correlations between inflammation and cancer progression have been shown. Endothelial cells (ECs), as part of the tumour microenvironment, play a crucial role in inflammatory processes as well as in angiogenesis and could be critical targets of cancer therapy like irradiation. Therefore, in the present study we investigated the effect of ionizing radiation on endothelial cells under inflammatory conditions and their interactions with tumour cells. Methods: Nonactivated and TNF-α treatment-activated human EC EA.hy926 were irradiated with doses between 0.1 Gy and 6 Gy with a linear accelerator. Using a multiplex assay, the accumulation of various chemokines (IL-8, MCP-1, E-selectin, and P-selectin) and soluble adhesion molecules (sICAM-1 and VCAM-1) as well as protein values of the vascular endothelial growth factor (VEGF) was measured in the supernatant at different time points. The adhesion capability of irradiated and nonirradiated A549 tumour cells to EA.hy926 cells was measured using flow cytometry, and the migration of tumour cells was investigated with a scratch motility assay. Results: In contrast to unirradiated cells, IR of ECs resulted in a modified release of chemokines IL-8 and MCP-1 as well as the adhesion molecules sICAM-1 and VCAM-1 in the EC, whereas concentrations of E-selectin and P-selectin as well as VEGF were not influenced. IR always affected the adhesion capability of tumour cells to ECs with the effect dependent on the IR-treated cell type. TNF-α treatment generally increased adhesion ability of the tumour cells. Tumour cell migration was clearly inhibited after IR. This inhibitory effect was eliminated for radiation doses from 0.5 to 2 Gy when, additionally, an inflammatory environment was predominant. Conclusions: Our results support past findings suggesting that ECs, as part of the inflammatory microenvironment of tumours, are important regulators of the actual tumour response to radiation therapy.


Assuntos
Comunicação Celular/efeitos da radiação , Células Endoteliais/metabolismo , Células Endoteliais/efeitos da radiação , Radiação Ionizante , Células A549 , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
Int J Occup Med Environ Health ; 32(5): 663-675, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31588928

RESUMO

OBJECTIVES: Interventional cardiologists (ICs) are occupationally exposed to low or moderate doses of ionizing radiation from repeated exposures. It is not clear whether these occupational conditions may affect their eye lens. Therefore, the risk of radiation-induced cataract in the cohort of Polish interventional cardiologists is analyzed in this paper. MATERIAL AND METHODS: The study group consisted of 69 interventional cardiologists and 78 control individuals occupationally unexposed to ionizing radiation. The eye lens opacities were examined using a slit camera and evaluated with Lens Opacities Grading System III. Cumulative eye lens doses were estimated retrospectively using a questionnaire including data on occupational history. RESULTS: The average cumulative dose to the left and right eye lens of the ICs was 224 mSv and 85 mSv, respectively. Nuclear opalescence and nuclear color opacities in the most exposed left eye were found in 38% of the ICS for both types, and in 47% and 42% of the controls, respectively. Cortical opacities were found in 25% of the ICS and 29% of the controls. Posterior subcapsular opacities were rare: about 7% in the ICs group and 6% in the control group. Overall, there was some, but statistically insignificant, increase in the risk for opacity in the ICs group, relative to the control group, after adjusting for the subjects' age, gender, smoking status and medical exposure (adjusted OR = 1.47, 95% CI: 0.62-3.59 for the pooled "any-eye any-type" opacity). There was also no evidence for an increased opacity risk with an increase in the dose. CONCLUSIONS: The study found no statistically significant evidence against the hypothesis that the risk of cataract in the group of the ICs occupationally exposed to low doses of ionizing radiation is the same as in the control group. Nevertheless, the adverse effect of ionizing radiation still cannot be excluded due to a relatively small study sample size. Int J Occup Med Environ Health. 2019;32(5):663-75.


Assuntos
Cardiologistas , Catarata/epidemiologia , Cristalino/efeitos da radiação , Exposição Ocupacional/efeitos adversos , Radiação Ionizante , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Radiografia/efeitos adversos , Estudos Retrospectivos , Inquéritos e Questionários
16.
BMC Cancer ; 19(1): 958, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619190

RESUMO

BACKGROUND: We analyzed the changes in permeability of endothelial cell layers after photon irradiation, with a focus on the metalloproteases ADAM10 and ADAM17, and on VE-cadherin, components crucial for the integrity of endothelial intercellular junctions, and their roles in the transmigration of cancer cells through endothelial cell monolayers. METHODS: Primary HUVEC were irradiated with 2 or 4 Gy photons at a dose rate of 5 Gy/min. The permeability of an irradiated endothelial monolayer for macromolecules and tumor cells was analyzed in the presence or absence of the ADAM10/17 inhibitors GI254023X and GW280264X. Expression of ADAM10, ADAM17 and VE-Cadherin in endothelial cells was quantified by immunoblotting and qRT. VE-Cadherin was additionally analyzed by immunofluorescence microscopy and ELISA. RESULTS: Ionizing radiation increased the permeability of endothelial monolayers and the transendothelial migration of tumor cells. This was effectively blocked by a selective inhibition (GI254023X) of ADAM10. Irradiation increased both, the expression and activity of ADAM10, which led to increased degradation of VE-cadherin, but also led to higher rates of VE-cadherin internalization. Increased degradation of VE-cadherin was also observed when endothelial monolayers were exposed to tumor-cell conditioned medium, similar to when exposed to recombinant VEGF. CONCLUSIONS: Our results suggest a mechanism of irradiation-induced increased permeability and transendothelial migration of tumor cells based on the activation of ADAM10 and the subsequent change of endothelial permeability through the degradation and internalization of VE-cadherin.


Assuntos
Proteína ADAM10/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Células Endoteliais/efeitos da radiação , Células Endoteliais da Veia Umbilical Humana/efeitos da radiação , Proteínas de Membrana/metabolismo , Proteólise/efeitos da radiação , Radiação Ionizante , Migração Transendotelial e Transepitelial/efeitos da radiação , Proteína ADAM10/antagonistas & inibidores , Proteína ADAM10/genética , Proteína ADAM17/antagonistas & inibidores , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/genética , Linhagem Celular Tumoral , Dipeptídeos/farmacologia , Células Endoteliais/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Permeabilidade/efeitos da radiação , Radioterapia/efeitos adversos , Transdução de Sinais/efeitos da radiação , Migração Transendotelial e Transepitelial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia
17.
Int J Mol Sci ; 20(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597345

RESUMO

Among the radicals (hydroxyl radical (•OH), hydrogen atom (H•), and solvated electron (esol-)) that are generated via water radiolysis, •OH has been shown to be the main transient species responsible for radiation damage to DNA via the indirect effect. Reactions of these radicals with DNA-model systems (bases, nucleosides, nucleotides, polynucleotides of defined sequences, single stranded (ss) and double stranded (ds) highly polymeric DNA, nucleohistones) were extensively investigated. The timescale of the reactions of these radicals with DNA-models range from nanoseconds (ns) to microseconds (µs) at ambient temperature and are controlled by diffusion or activation. However, those studies carried out in dilute solutions that model radiation damage to DNA via indirect action do not turn out to be valid in dense biological medium, where solute and water molecules are in close contact (e.g., in cellular environment). In that case, the initial species formed from water radiolysis are two radicals that are ultrashort-lived and charged: the water cation radical (H2O•+) and prethermalized electron. These species are captured by target biomolecules (e.g., DNA, proteins, etc.) in competition with their inherent pathways of proton transfer and relaxation occurring in less than 1 picosecond. In addition, the direct-type effects of radiation, i.e., ionization of macromolecule plus excitations proximate to ionizations, become important. The holes (i.e., unpaired spin or cation radical sites) created by ionization undergo fast spin transfer across DNA subunits. The exploration of the above-mentioned ultrafast processes is crucial to elucidate our understanding of the mechanisms that are involved in causing DNA damage via direct-type effects of radiation. Only recently, investigations of these ultrafast processes have been attempted by studying concentrated solutions of nucleosides/tides under ambient conditions. Recent advancements of laser-driven picosecond electron accelerators have provided an opportunity to address some long-term puzzling questions in the context of direct-type and indirect effects of DNA damage. In this review, we have presented key findings that are important to elucidate mechanisms of complex processes including excess electron-mediated bond breakage and hole transfer, occurring at the single nucleoside/tide level.


Assuntos
Nucleosídeos/química , Radiólise de Impulso , Elétrons , Nucleotídeos/química , Fosfatos/química , Radiação Ionizante , Soluções , Açúcares/química , Água/química
18.
Exp Oncol ; 41(3): 224-234, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31569932

RESUMO

In this review, literature data on the study of precancerous changes in testicular tissue and molecular changes, as well as the influence of environmental factors that can initiate carcinogenesis, were analyzed and summarized for the future determination of early diagnosis of germ cell tumors of the testis and the development of preventive measures. The review also discusses the significant new changes presented in the Fourth Edition of the World Health Organization Classification of Urogenital Tumors, published in 2016, and modern concepts of the etiology and pathogenesis of these diseases. Among the environmental factors that can initiate carcinogenesis, the most noteworthy are the biological effects of low doses of ionizing radiation, such as the effect of radiation-induced genome instability, which increases the risk of carcinogenesis, the "bystander effect", and chronic oxidative stress. Disruption of ubiquitin-proteasomal proteolysis, impaired molecular-level components of the blood-testis barrier, and impaired regulatory action of TGF-ß on the cell cycle can play a crucial role in the pathogenesis of male infertility and the initiation of carcinogenesis in the testis. The effect of low doses of ionizing radiation as an additional etiological factor leads to changes in the structural, as well as molecular, components of the testis, including epigenetic changes, which can be characterized as environmental pathomorphosis, which leads to impaired spermatogenesis and increased risk of malignancy. Summarizing the literature review data, we can state that patients with blocked spermatogenesis, in which atypical germ cell neoplasia in situ cells are detected in testicular tissue, constitute a group at increased risk of testicular carcinogenesis. The presence of additional etiological factors, such as chronic low doses of ionizing radiation, can initiate the progression of carcinogenesis in the testicle.


Assuntos
Transformação Celular Neoplásica , Neoplasias Testiculares/etiologia , Neoplasias Testiculares/metabolismo , Testículo/metabolismo , Testículo/patologia , Biomarcadores , Barreira Hematotesticular/metabolismo , Humanos , Masculino , Modelos Biológicos , Radiação Ionizante , Espermatogênese , Neoplasias Testiculares/patologia , Testículo/efeitos da radiação , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismo
19.
Lett Appl Microbiol ; 69(5): 333-338, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31536642

RESUMO

Due to increasing antibiotic resistance Klebsiella pneumoniae is a serious threat for the hospitalized patients. The aim of this study was the assessment of radiant catalytic ionization (RCI) efficacy on K. pneumoniae reduction in the air and on selected surfaces. Four K. pneumoniae NDM and ESBLs-producing strains were included in the study. Three types of surface were tested: cotton-polyester, terry and PVC. It was found that RCI significantly reduced the number of bacteria from all types of surface (terry: 0·56-1·22 log CFU m2 , cotton-polyester: 2·15-3·71 log CFU per m2 , PVC: 4·45-4·92 log CFU per m2 ) as well as from the air (1·80 log CFU per m3 ). The RCI technology may be a useful disinfection method in hospitals. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial contamination of air and surfaces in hospitals play an important role in healthcare-associated infections. The aim was the assessment of Klebsiella pneumoniae elimination using radiant catalytic ionization (RCI). K. pneumoniae are aetiological agent of nosocomial infections, such as: pneumonia, infections of urinary tract, blood, e.t.c. The strains producing the New Delhi metallo-ß-lactamases are one of the greatest epidemiological threat. The use of RCI eliminate the tested bacteria from the hospital environment, but can also be effective in food processing plants or public facilities, ensuring the safety of people and products. This research is scarce in references and has a large innovation and application potential.


Assuntos
Proteínas de Bactérias/metabolismo , Infecção Hospitalar/prevenção & controle , Infecções por Klebsiella/prevenção & controle , Klebsiella pneumoniae/efeitos da radiação , beta-Lactamases/metabolismo , Microbiologia do Ar , Proteínas de Bactérias/genética , Infecção Hospitalar/microbiologia , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/crescimento & desenvolvimento , Viabilidade Microbiana/efeitos da radiação , Radiação Ionizante
20.
Adv Exp Med Biol ; 1167: 225-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520358

RESUMO

Ionizing radiation (IR) is used to treat more than half of human cancer patients. The therapeutic effect of IR is due to its ability to induce apoptosis. Success of radiation therapy relies not only on apoptosis induction but also on whether surviving cancer cells proliferate and regenerate a tumor. Drosophila melanogaster is a premier genetic model and, relevant to radiation biology of cancer, Drosophila larvae display an amazing capacity to regenerate. IR doses that kill more than half of the cells in larval tissues still allow complete regeneration to produce an adult fly of normal size and pattern. It is by understanding not only the initial effects of IR such as DNA damage and cell death but also longer-term regenerative responses that we may manipulate and improve radiation therapy of cancer. In this regard, Drosophila offers an unparalleled model to study both types of responses.


Assuntos
Drosophila melanogaster , Neoplasias/radioterapia , Animais , Apoptose , Modelos Animais de Doenças , Humanos , Radiação Ionizante , Radiobiologia
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